Your Digest for Monday, Apr 22, 2024 02:59 PM

Phase I - double digits (<100)
Phase II - Triple digits (<300)
Phase III - quadruple digits, also C being the 3rd letter of the alphabet, phase III trials 'compare' efficacy -> RCTs. (<3000)
3. Phamacokinetic testing to determine ADME characteristics (absorption, distribution, metabolism and elimination)
Phase 3 = 1000-3000 to confirm effectiveness, monitor side effects and compare with other treatments. (⭐therapeutic confirmation - Randomized controlled trials; efficacy, safety)

[!INFO] Mmemonic: Bag of flowers
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• Isolated systolic hypertension is the predominant form of hypertension in the elderly population.
• develops as a result of the reduced elasticity of the arterial system.
• commonly seen among the elderly as there is increased deposition of calcium and collagen to the arterial wall

• most common cause of blindness in young men
  ++ /dev/null

• Reprogramming of stem cells to differentiate into a cell type that is more suitable to cope with the new stresses than the original cell type at that location. Can occur in epithileal OR mesenchyal cells.
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• Disorderly, but non neoplastic proliferation.

Other causes of subtotal villous atrophy

• CVID can also cause SVA.

• Cyst is the infective stage. (Cysts are immediately infectious upon excretion, they can survive chlorinated water)
• Cyst are ingested via contaminated water or food (like salads). Faeco-oral person to person transmission can occur (eg. Child care centers)
• Abdominal pain, watery diarrhea, weight loss.
• Severe infection can invade the mucosa in severe infection but usually there is no invasion.
• Treatment: tinidazol, ⭐metronidazole is second line due to concern of side effects. Achieves parasite clearance within 1 week.

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Source
Pharmacological efficacy (also called Intrinsic efficacy) is

[[2018-OCT-BSQ#Pulmonary vascular resistance]]

• But ⭐80% of NALFD patients have normal liver enzymes. Source

Pathophysiology of NAFLD

Insulin resistance is the key prerequisite for NAFLD.

• ⭐Steatosis (fatty change), Hepatitis (inflammation) and Fibrosis
• Starts with fat accumulation in centrilobular areas and then spreads outwards. The liver will be soft, yellow and greasy. (i.e starts in ZONE 3)
• Steatosis is ⭐macrovessicular.
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• Hepatocyte ballooning with necrosis
• Intracellular eosinophilic includions: ⭐Mallory Denk bodies
• 
• ⭐Neutrophil infiltration to remove the necrotic hepatocytes and those with Mallory Denk bodies.
  Fibrosis
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• Also appears in zone 3 and spread outwards. (⭐central vein sclerosis)
• Perisinusoidal scarring in space of disse also similarly spreads outwards. [[HepaticSinusoidSpaceOfDisse.jpg]]
• These changes cause ⭐micronodular cirrhosis. (aka Laennec cirrhosis)
• Mild increases in ALT and AST with ALT > AST; mild elevation of ⭐gamma-GT. (don't be mislead into thinking it's alcoholic hepatitis)
• Elastography - to evaluate degree of fibrosis.
• Absolute mainstay of treatment: Lifestyle advice aimed at weight loss with exercise and dieting.
• Orlistat (enteric lipase inhibitor) is used as adjunct in severely obese to reduce intestinal lipid absorption
  • Can cause vitamin malabsorption.
  • Pioglitazone has been proven to reduce NASH but weight gain CCF, bladder cancer and fracture risk are increased.
    Source

4. Dyslipidaemia (Low HDL and high TGL)